This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A central goal of diabetes research (type 1 and type 2) is to generate large numbers of functional pancreatic islets or beta-cells for replacement therapy. Therefore, a fundamental knowledge of mechanisms and factors that promote beta-cell regeneration is essential for planning strategies to preserve and enhance beta-cell mass in vivo or to generate beta-cells in vitro for transplantation. This project applies quantitative proteomics approaches to identify new blood circulatory factors and islet proteins involved in beta-cell proliferation in a unique mouse model, the liver-specific insulin receptor knockout (LIRKO) mouse, which exhibit 20- to 30-fold increase in beta-cell mass in response to insulin resistance. This project requires high sensitivity, high resolution LC-FTICR capability from the resource for comparative quantitative characterization of the pancreatic islet proteins and serum proteins from mice with liver specific knockout of insulin receptor (LIRKO).